Structure-Activity and Interaction Effects of 14 Different Pyrethroids on Voltage-Gated Chloride Ion Channels

Abstract

We have proposed that since the type II pyrethroids deltamethrin and cypermethrin, but not the type I pyrethroid cismethrin act on chloride channels, this could contribute to the bimodal nature of pyrethroid poisoning syndromes. We now examine a wider range of pyrethroid structures on the activity of these calcium-independent voltage-gated maxi-chloride channels. Excised inside-out membrane patches from differentiated mouse neuroblastoma cells were used, and mean channel open probabilities calculated. For single dosing at 10 microM, bioallethrin, beta-cyfluthrin, cypermethrin, deltamethrin, and fenpropathrin were all found to significantly decrease open channel probability (p < 0.05). Bifenthrin, bioresmethrin, cispermethrin, cisresmethrin, cyfluthrin isomers 2 and 4, lambda-cyhalothrin, esfenvalerate, and tefluthrin, did not significantly alter open channel probability (p > 0.05). Since the type II pyrethroids, esfenvalerate, and lambda-cyhalothrin were ineffective, we must conclude that actions at the chloride ion channel target cannot in themselves account for the differences between the two types of poisoning syndrome. Sequential dosing with type II pyrethroids caused no further chloride ion channel closure. The type I pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed type pyrethroid fenpropathrin. In contrast, the type I pyrethroid cispermethrin did not prevent a subsequent effect due to the type II pyrethroid deltamethrin. The difference in effect may be the result of differences in potency, as deltamethrin had a greater effect than fenpropathrin. It therefore appears clear that in some combinations the type I and type II pyrethroids can compete and may bind to the same chloride channel target site.

Effects of a cypermethrin-based pesticide on early life stages of common carp (Cyprinus carpio L.)

“…Cypermethrin blocks sodium channels of nerve filaments by lengthening their depolarisation phase as well as affecting gamma-aminobutyric acid receptors and chloride and calcium channels in nerve filaments (Bradbury and Coats 1989b;Hayes 1994;Burr and Ray 2004). Cypermethrin contains chlorine atoms in a vinyl side chain of the compound.…”

Deltamethrin, a Pyrethroid Insecticide, Is a Potent Inducer for the Activity-Dependent Gene Expression of Brain-Derived Neurotrophic Factor in Neurons

“…Pyrethroids prolong the opening of the voltage-sensitive sodium channel (VSSC) and raise a prolonged sodium tail current in mammalian as well as invertebrate neurons (Vijverberg et al, 1982;Narahashi, 1985). Furthermore, it has been reported that pyrethroids act on not only VSSC but also other ion channels or neurotransmitter receptors, such as voltagegated chloride channels (Burr and Ray, 2004) and GABA A receptors (Crofton and Reiter, 1987). In contrast, we have already demonstrated that relatively high concentrations (more than 10 M) of pyrethroid insecticides decreased the expression of c-fos and BDNF genes induced by membrane depolarization in mouse cerebellar granule cells (Imamura et al, 2000).…”

Insecticide Groups and Their Effects in Aquatic Environment

“…While excretion of various pyrethroids in the birds and mammals is about 6-12 hours, it is 48 hours in the trout. Like all pyrethroids "Bifenthrin" is highly toxic to fish, interfering with Na + channel gating in the nerve cell endings, but other ion channels such as Cl -and Ca + channels can be targeted as well [37]. This leads to continuous neurotransmission causing hyperexcitability, tremors, convulsions and finally death.…”